Upper-body obesity is associated with a greater risk of metabolic complications than lower-body obesity. The factors that determine regional fat distribution in humans are not known, but must relate to regional differences in adipose tissue fatty acid uptake and/or release. We have measured regional adipose tissue FFA release in non-obese men and women and in upper-body and lower-body obesity. Our results do not support the hypothesis that basal or meal related differences in regional lipolysis are important determinates of body fat distribution, but suggest that regional differences in exercise-stimulated lipolysis may contribute in a minor way to preferential lower-body fat accumulation in women. We believe that regional variations in adipose tissue fatty acid uptake are likely to be important determinants of fat distribution and should now be carefully studied using in vivo techniques. Understanding the contribution of regional differences in adipose tissue fatty acid uptake and FFA release to regional fat distribution should allow more productive and focused studies of the environmental, hormonal, and genetic determinants of body fat distribution and, therefore, the health consequences of obesity. The objectives of this proposal are to determine whether regional differences in exercise-stimulated lipolysis could influence body fat distribution, expand and fully define the use of the meal tracer/adipose tissue biopsy technique to study meal fatty acid disposal in humans, and assess the effects of gender, body fat distribution in obesity, overfeeding, and underfeeding on meal fatty acid disposal. Specifically, these studies will determine whether: 1) Exercise stimulates lower-body adipose tissue FFA release in men, but not women. 2) Non-obese men have greater upper-body subcutaneous adipose tissue meal fatty acid uptake than non-obese women. 3) Meal fatty acid uptake and oxidation is different in the follicular versus luteal phase of the menstrual cycle. 4) Gender related differences in meal fatty acid oxidation and adipose tissue uptake can be accounted for by differences in body composition. 5) Consuming a larger meal specifically increases abdominal subcutaneous adipose tissue meal fatty acid uptake in individuals with an android as opposed to a gynoid fat distribution. 6) Weight loss induced by energy restricted diets results in decreased meal fatty acid oxidation and increased meal fatty acid uptake in subcutaneous adipose tissue.